Human milk is the preferred means for feeding the newborn human infant for the first four to six months of life. Infant formulas have been developed to replace or to supplement human milk when breast-feeding is inadequate, unsuccessful, or when a mother chooses not to breast feed. Attempts of improving infant formula composition have focused on more closely simulating the composition of breast milk.
Bovine milk has been used in infant formulas for over eighty years. However, the protein systems of human milk and cow's milk differ substantially, both quantitatively and qualitatively. Prominent quantitative differences include a lower total protein content of human milk (11 g/L) compared to cow's milk (33 g/L) and a difference in the ratio of whey proteins to caseins, which is 18:82 in bovine milk and 60:40 in human milk.
Attention in this area has focused on the notable qualitative differences between bovine milk and human milk, in their amounts of individual whey proteins, specifically alpha-lactalbumin and beta-lactoglobulin. Alpha-lactalbumin, a protein found in the milk of all mammals, is a major protein in human milk. Beta-lactoglobulin is absent from human milk. The protein content of bovine whey contains about 50% to 55% of beta-lactoglobulin and about 18% of alpha-lactalbumin. The ratio of beta-lactoglobulin to alpha-lactalbumin in bovine whey ranges between 2.5:1 and 4:1. Furthermore, it is known that the elimination or removal of beta-lactoglobulin in bovine milk increases the total amount of alpha-lactalbumin from 18% to 40% of bovine whey proteins, de Wit, J. N., “Nutritional and Functional Characteristics of Whey Proteins in Food Products”, Journal of Dairy Science 81: 597-608 (1998).
Beta-lactoglobulin is particularly rich in the essential amino acids valine and threonine. Alpha-Lactalbumin is particularly rich in the essential amino acids tryptophan, lysine and cystine compared to other bovine milk proteins, Jarvenpaa, A. L., N. C. Raiha, et al., “Milk protein quantity and quality in the term infant. I. Metabolic responses and effects on growth”, Pediatrics 70(2): 214-20 (1982). As a consequence of the differing amounts of the specific whey proteins in bovine milk and human milk and the amino acid compositions of these proteins, bovine milk and human milk differ substantially in their amino acid profiles, Rudloff, S. and C. Kunz, “Protein and nonprotein nitrogen components in human milk, bovine milk, and infant formula: quantitative and qualitative aspects in infant nutrition”, J Pediatr Gastroenterol Nutr 24(3): 328-44 (1997). This difference remains in infant formulas made with bovine whey in which the composition of the specific whey protein is not modified.
As noted above, the elimination or reduction of beta-lactoglobulin in cow's milk-based infant formula increases the content of alpha-lactalbumin. Such a change would subsequently increase the levels of the essential amino acids cystine, tryptophan, tyrosine and phenylalanine and reduce the level of the essential amino acid threonine to levels that more closely resemble those in human milk. Therefore, an improved amino acid composition would permit a reduction in the total protein content of an infant formula.
DeWit, de Wit, J. N., “Nutritional and Functional Characteristics of Whey Proteins in Food Products”, Journal of Dairy Science 81: 597-608 (1998), describe research activities focused on the fine-tuning of both milk protein and amino acid composition and specifically on enriching bovine milk with alpha-lactalbumin, beta-casein and lactoferrin to achieve the optimal nutritional composition, particularly with respect to the amino acid composition thereof. A nutritional composition is proposed which comprises beta-lactoglobulin-depleted whey proteins, beta-casein and lactoferrin in desalted bovine milk permeate. It is postulated that such a preparation will have a protein composition more closely approaching that of human milk than existing infant formulas.
Dairy technology has focused on whey protein fractionation processes to selectively remove substantially all the beta-lactoglobulin from whey or to isolate enriched alpha-lactalbumin fractions substantially free of beta-lactoglobulin, for use in foods, including infant formula. U.S. Pat. No. 5,455,331 describes a process using undefatted ultrafiltered whey to produce a material with a high alpha-lactalbumin content and, on a total precipitable protein basis, less than 5% of beta-lactoglobulin. The process involves heat precipitation of alpha-lactalbumin in undefatted ultrafiltered cheese whey at a pH of 4.2. The alpha-lactalbumin-rich precipitate is clarified, washed, neutralized, ultrafiltered and spray dried to yield a whey fraction, the protein therein being predominantly alpha-lactalbumin, substantially depleted of beta-lactoglobulin and including the lipid-containing components in the whey.
U.S. Pat. No. 5,420,249 discloses the use of defatted whey and calcium-binding resin to prepare whey for separation and a preferred alpha-lactalbumin fraction comprising at least 60% of the protein as alpha-lactalbumin and at most 10% of the protein as beta-lactoglobulin. They describe an alpha-lactalbumin-enriched fraction containing 13% of the protein as beta-lactoglobulin. However, this fraction contained 74% of the protein as alpha-lactalbumin, with a beta-lactoglobulin to alpha-lactalbumin ratio of 1:6. Other alpha-lactalbumin-enriched fractions had beta-lactoglobulin to alpha-lactalbumin ratios of 1:4 to 1:7.
U.S. Pat. No. 5,436,020 describes an infant formula devoid of untreated cows' milk protein which is made with a material consisting of delactosed and deionized whey permeate as a source of non-protein nitrogen combined with a fractionated whey ultrafiltered to remove casein glycomacropeptides and fat. U.S. Pat. No. 5,169,666 describes treating bovine milk to eliminate or substantially reduce the alpha-s-casein and to reduce the beta-lactoglobulin level to 4% or less as a percentage of the protein, in order to make a ‘humanized’ bovine milk material for infant feeding.